Article : Transmitted and Acquired Antiretroviral Resistance...

Transmitted and Acquired Antiretroviral Resistance — An Intriguing Analysis

Charles B. Hicks, MD reviewing Yang W-L et al. J Infect Dis 2015 Jan 9.


Analysis of resistance data from the Swiss HIV Cohort suggests different sources for the various resistance mutations, with viral fitness the key factor.

Although rates of acquired antiretroviral drug resistance (ADR) have declined in association with the improved effectiveness of contemporary antiretroviral therapy (ART), the overall prevalence of transmitted drug resistance (TDR) has remained relatively unchanged. Now, using Swiss HIV Cohort data from 1998 through 2012, researchers have investigated factors driving both ADR and TDR, with a focus on recently infected, ART-naive individuals.

Overall, the ADR rate among ART-experienced patients peaked at 85% in 1998, then fell continuously to a new plateau of ~38% in 2009. In contrast, during the same period, the overall TDR rate among ART-naive patients increased by about 0.3% per year. Among recently infected, ART-naive patients, TDR prevalence fell substantially after the introduction of new drug classes (particularly boosted protease inhibitors and integrase inhibitors) but increased over time in the absence of new classes.

To identify factors associated with TDR, commonly identified mutations were analyzed: M184V and K103N in genes encoding reverse transcriptase and L90M in those encoding protease. The prevalence of M184V as a transmitted mutation correlated with population plasma viral load among patients failing ART with M184V (presumed source patients). No such relationship was seen with L90M or K103N, suggesting that these mutations were transmitted from recently infected, treatment-naive individuals with founder viruses carrying L90M or K103N.


Citation(s):

Yang W-L et al. Assessing the paradox between transmitted and acquired HIV-1 drug resistance in the Swiss HIV Cohort Study from 1998 to 2012. J Infect Dis 2015 Jan 9; [e-pub ahead of print].

BACK